Extracellular regulation of metalloproteinases

Kazuhiro Yamamoto, Gillian Murphy, Linda Troeberg

Research output: Contribution to journalReview articlepeer-review

103 Citations (Scopus)
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Abstract

Matrix metalloproteinases (MMPs) and adamalysin-like metalloproteinase with thrombospondin motifs (ADAMTSs) belong to the metzincin superfamily of metalloproteinases and they play key roles in extracellular matrix catabolism, activation and inactivation of cytokines, chemokines, growth factors, and other proteinases at the cell surface and within the extracellular matrix. Their activities are tightly regulated in a number of ways, such as transcriptional regulation, proteolytic activation and interaction with tissue inhibitors of metalloproteinases (TIMPs). Here, we highlight recent studies that have illustrated novel mechanisms regulating the extracellular activity of these enzymes. These include allosteric activation of metalloproteinases by molecules that bind outside the active site, modulation of location and activity by interaction with cell surface and extracellular matrix molecules, and endocytic clearance from the extracellular milieu by low-density lipoprotein receptor-related protein 1 (LRP1).

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalMatrix Biology
Volume44-46
Early online date18 Feb 2015
DOIs
Publication statusPublished - 24 Feb 2015

Keywords

  • ADAM Proteins/chemistry
  • Allosteric Regulation
  • Binding Sites
  • Cell Membrane/enzymology
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Matrix Metalloproteinases/chemistry

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